Systemic treatment in triple-negative breast cancer patients — standard and novel approaches

Abstract

In recent years, after a long standstill in pharmacotherapy of triple-negative breast cancer (TNBC), several new targeted agents have been registered for treatment of patients with this neoplasm (pembrolizumab, olaparib, talazoparib, sacituzumab govitecan, and trastuzumab deruxtecan). The standard treatment for patients with early TNBC and operable primary tumors up to 2 cm and negative lymph nodes is primary surgery followed by adjuvant chemotherapy and possible radiotherapy. Patients with higher local and regional stages are candidates for primary chemotherapy followed by radical surgery and adjuvant treatment. Adjuvant olaparib prolongs invasive disease-free survival and overall survival of patients with germline BRCA1/2 mutation. Adding pembrolizumab to perioperative systemic treatment increases the pathological complete response rate (pCR) and prolongs event-free survival. However, there are no data on effectiveness and safety of applying combined immunotherapy with adjuvant capecitabine for patients without pCR after preoperative treatment or with adjuvant olaparib for germline BRCA1/2 mutation carriers. Chemotherapy is the standard treatment for advanced TNBC. Palliative treatment with PARP inhibitors (olaparib, talazoparib) in patients with germline BRCA1/2 mutation prolongs progression-free survival and increases the overall response rate compared with chemotherapy. In PD-L1-positive patients, adding pembrolizumab to first-line chemotherapy increases the response rate and prolongs survival. The same endpoints are better for TNBC patients treated with sacituzumab govitecan compared with chemotherapy. Trastuzumab deruxtecan is indicated for the treatment of patients with low human epidermal growth factor receptor 2 (HER2) expression and is more efficient than chemotherapy. In Poland, pembrolizumab, talazoparib, and sacituzumab govitecan are reimbursed from public funds.